title: The mechanism underlying the synergetic hypocholesterolemic effect of sesamin and α-tocopherol in rats fed a high-cholesterol diet.
abstract: Sesamin is a major lignan in sesame seed. We confirmed that ingestion of sesamin and α-tocopherol synergistically reduced the concentration of blood cholesterol in rats given a high-cholesterol diet. To elucidate the molecular mechanism behind this effect, we analyzed the gene-expression profiles in rat liver after co-ingestion of sesamin and α-tocopherol. Six-week-old male Sprague-Dawley rats were fed a 1% cholesterol diet (HC) or HC containing 0.2% sesamin, 1% α-tocopherol or sesamin + α-tocopherol for 10 days. Blood samples were collected on days 1, 3, 7, and 10 and livers were excised on day 10. The gene expressions of ATP-binding cassette, sub-family G (WHITE), members 5 (ABCG5) and 8 (ABCG8) were significantly increased, while the gene expression of apolipoprotein (Apo) A4 was significantly decreased. ABCG5 and ABCG8 form a functional heterodimer that acts as a cholesterol efflux transporter, which contributes to the excretion of cholesterol from the liver. ApoA4 controls the secretion of ApoB, which is a component of low-density-lipoprotein cholesterol. These studies indicate that the cholesterol-lowering mechanism underlying the effects of co-ingestion of sesamin and α-tocopherol might be attributable to increased biliary excretion of cholesterol and reduced ApoB secretion into the bloodstream.
authors.affiliation: Institute for Health Care Science, Suntory Wellness Limited, Osaka, Japan. Tomohiro_Rogi@suntory.co.jp
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Rogi
authors.forename: Namino
authors.initials: N
authors.lastname: Tomimori
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Ono
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kiso
mesh_terms: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D001054:Apolipoproteins A / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000097:blood*; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D008078:Cholesterol, LDL / Q000097:blood*; D004036:Diet, Atherogenic; D004149:Dioxoles / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D017705:Lignans / Q000008:administration & dosage / Q000494:pharmacology*; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; C480692:Abcg5 protein, rat; C480693:Abcg8 protein, rat; D000924:Anticholesteremic Agents; D000975:Antioxidants; D001054:Apolipoproteins A; D002791:Cholesterol, Dietary; D008078:Cholesterol, LDL; D004149:Dioxoles; D017705:Lignans; D008074:Lipoproteins; C022205:apolipoprotein A-IV; D002784:Cholesterol; D024502:alpha-Tocopherol; C054125:sesamin